B细胞激活因子
子痫前期
血管紧张素II
CD40
血管紧张素Ⅱ受体1型
内分泌学
内科学
医学
氯沙坦
细胞因子
免疫学
B细胞
抗体
化学
受体
生物
细胞毒性T细胞
生物化学
怀孕
体外
遗传学
作者
Owen Herrock,Evangeline Deer,Lorena M. Amaral,Nathan Campbell,Darby Whitney,Nicole Ingram,Denise C. Cornelius,Ty Turner,Ja'Nasa Hardy-Hardin,George W. Booz,Tarek Ibrahim,Babbette LaMarca
摘要
Preeclampsia (PE), new-onset hypertension during pregnancy, is associated with a pro-inflammatory state with activated T cells, cytolytic natural killer (NK) cells, dysregulated complement proteins, and B cells secreting agonistic autoantibodies to the angiotensin II type-1 receptor (AT1-AA). The reduced uterine perfusion pressure (RUPP) model of placental ischemia recapitulates these features of PE. Blocking CD40L-CD40 communication between T and B cells or B cell depletion with Rituximab prevents hypertension and AT1-AA production in RUPP rats. This suggests that T cell-dependent B cell activation contributes to the hypertension and AT1-AA associated with PE. B2 cells maturing into antibody producing plasma cells are the product of T cell-dependent B cell-interactions and B cell Activating Factor (BAFF) is an integral cytokine in the development of B2 cells specifically. Thus, we hypothesize that BAFF blockade will selectively deplete B2 cells, therefore reducing blood pressure, AT1-AA, activated NK Cells, and complement in the RUPP rat model of PE.Gestational Day (GD) 14 pregnant rats underwent the RUPP procedure, and a subset were treated with 1 mg/kg Anti-BAFF antibodies via jugular catheters. On GD19, blood pressure was measured, B cells and NK cells were measured by flow cytometry, AT1-AA was measured by cardiomyocyte bioassay, and complement activation was measured by ELISA.Anti-BAFF therapy attenuated hypertension, AT1-AA, NK cell activation, and APRIL levels in RUPP rats without negatively impacting fetal outcomes.This study demonstrates that B2 cells contribute to hypertension, AT1-AA, and NK cell activation in response to placental ischemia during pregnancy.
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